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T
he Pathogenic Mechanisms group

The Pathogenic Mechanisms group characterises the molecular mechanisms deployed by bacteria in order to colonise, survive and multiply during infection. By identifying and characterising the mechanisms that a bacterium uses to ensure its survival and persistence in a human or animal, these molecular activities can then be targeted for the development of antimicrobials and therapeutics.

The Pathogenic Mechanisms group utilises molecular techniques and facilities to investigate the relationships between bacteria and the cells of humans and animals. The balance of bacterial pathogenic mechanisms versus the host immune resistance mechanisms determines whether the bacteria will be killed and eliminated from the host or whether the bacteria will survive in the host and multiply. Bacteria have evolved a myriad of ways by which they can tip the balance in their favour.

Several bacterial pathogens use Type III Secretion Systems (TTSS) to modulate host cell behaviour. TTSS directly channel effector proteins from bacteria into eukaryotic cells, where they cause dysfunctional regulation of eukaryotic cell signalling proteins and sabotage the normal processes of the cell, thereby enhancing the ability of the bacteria to colonise the host. For example, cytokine and chemokine production may be altered, epithelial barrier functions may be perturbed, or bactericidal mechanisms may be inhibited.

Our primary research focus is the TTSS of Vibrio parahaemolyticus which causes gastroenteritis after eating contaminated shellfish. V. parahaemolyticus has a severe detrimental economic impact on aquaculture, as well as being detrimental to human health. Our goal is to understand the molecular basis for the importance of TTSS in the pathogenicity of Vibrio species.

Investigating the effect of TTSS on host cell behaviour and how this facilitates bacterial survival

Identifying and characterising the adhesins that attach the bacteria onto host cells to facilitate colonisation and deployment of the TTSS

Studying the TTSS effectors and the eukaryotic proteins that they target in order to elucidate their mechanism of action

As well as increasing understanding of Vibrio pathogenesis, this research promotes a broader knowledge of TTSS and host manipulation by pathogenic organisms. It has the potential to lead to the development of the effector toxins as tools for cell biology research. Furthermore it could lead to the identification of candidate targets as diagnostic markers and for preventive and therapeutic antimicrobial strategies, thereby improving food safety and human health.